Halogen-alkyl amidines and process of preparing same



Patented Aug. 19, 1941 HALOGEN-ALKYL hummus AND F rnarAnmGsAMn PROCESS Karl Miescher and Willi Klarer, Riehenyand I Ernst Urech, Basel, switzerlanmassignors, by mesne assignments, to Cibalharmaceutical Products, Incorporated, Summit, N. J.,- a cor-. poration oi. New Jersey No Drawing. Application April 29, 1639, Serial No. 270,934. In Switzerland May 11, 1938 9 Claims.

This invention relates to the manufacture of new halogenalkylamidines by causing a halogencarboxylic acid derivative to react with an amine.

The compounds thus obtained may be supposed to comprise the following structure:

wherein A .is a halogen-alkyl radical. These new amidines may be open chain compounds or cyclic compounds. In the latter case the two amidine nitrogen atoms are united together by an alkylene chain, as for instance in the imidazoline ring or the tetrahydropyrimidine ring.

Among the aforesaid acid derivatives are for example the imido ethers obtainable from the nitriles, the imido halides corresponding with the amides or the thioamides.

As amines there come into question primary or secondary mono-amines and diamines, for instance ammonia, saturated and unsaturated alkylamines, alkylenediamines, aralkylamines, aromatic or heterocyclic amines, for instance anilines, naphthylamines, aminopyridines, aminoquinolines, aminobenzthiazoles or the like. There may also be used however amines in which the nitrogen is cyclic-bound, for instance as in' The products of the invention are valuable intermediates for synthetic products, for exam- 7 pie in the manufacture of pharmaceutical preparations.

The following examples illustrate tion, the parts being by weight:

Example 1 the inven- 157 parts of chloracetimidoethylether hydrochloride are added to an ice cooled solution of 60 parts of ethylenediamine in 800 parts or absolute alcohol whilst stirring well. After about /2 hour there is added a solution oi 36 parts of hydrogen chloride in 500 parts of absolute alcohol and the mixture is heated gradually to room temperature. The ammonium chloride produced is filtered and the clear filtrate is evaporated and the residue recrystallized from a little hot absolute alcohol, whereby the 2-chloromethyl-imidazoline hydrochloride is precipitated in the form of colorless crystals melting at 185-1900.

The reaction takes place in accordance with the following equation:

In similar manner the 2-bromomethyl-imidazoline may be made.

Emmple 2 ,185 parts of 'y-chlorobutyroimidoethyl ether hydrochloride (obtainable by the action of hydrogen chloride on a mixture of equivalent quantities of 'y-chlorobutyronitrile and ethyl alcohol) are introduced whilst cooling and stirring into a mixture of parts of ethylenediamine and 400 parts of absolute alcohol. There is then added a solution of 36 parts of hydrogen chloride in 360 parts or absolute alcohol and the mixture is further worked up as described in Example 1. By recrystallization from a'mixture 01 alcohol and ether the 2-('y-chloropropyl)-imidazoline hydrofiiorde is obtained in a pure state; it melts at The reaction takes place according to the following equation:

soluble portion is the chloracet-piperidineamidine hydrochloride of melting point 176 C.

The reaction takes place according to the fo lowing equation:

mar-101 CHI-CH! ol-om-c nN cm 5 OCzHs CHE-CH:

NHJICI ClCHr-C cmcm \N/ on, canon CHFC S Instead of the chloracetimidoethylether there may be used another ether.

What we claim is:

1. 2- (chloromethyl) -imidazoline forming a hydrochloride of melting point 1 85-190 C.

methylimidazoline, which comprises causing a chloroacetic acid imidoether to react with ethylenediamine.

5. The compounds of the formula wherein :0 represents an integer selected from the group consisting of 2 and 3.

6. The compounds of the formula N- C H:

halogenalkyl-C 7. The compounds of the formula NH halogenalkyl-O I wherein R1 represents a member of the group consisting of hydrogen, alkyl, aryl, aralkyl and a heterocyclic radical;

8. The compounds of the formula halogenalkyl-C N=Rz wherein R2 represents a chain of CH: groups, the terminal members of which are attached to the N-atom of the -N=Rz group.

9. The compounds of the formula halogenalkyl X wherein X represents a radical selected from the group consisting of and N=Ra as representing an integer from the group consisting of 2 and 3, R1 2. member of the group consisting of hydrogen, alkyl, aryl, aralkyl and a heterocyclic radical, and R: a chain of CH2 groups whose terminal members are attached to the N-atom of the N=R2 group.

KARL NHESCBER. WILLI KLARER. ERNST URECH. 

